rs764685377

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6

The NM_032119.4(ADGRV1):​c.3943C>A​(p.Gln1315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

4
14

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.31
Variant links:
Genes affected
ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26693225).
BP6
Variant 5-90653517-C-A is Benign according to our data. Variant chr5-90653517-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 504579.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADGRV1NM_032119.4 linkc.3943C>A p.Gln1315Lys missense_variant Exon 20 of 90 ENST00000405460.9 NP_115495.3 Q8WXG9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkc.3943C>A p.Gln1315Lys missense_variant Exon 20 of 90 1 NM_032119.4 ENSP00000384582.2 Q8WXG9-1
ADGRV1ENST00000640403.1 linkc.1234C>A p.Gln412Lys missense_variant Exon 10 of 29 5 ENSP00000492531.1 A0A1W2PRC7
ADGRV1ENST00000504142.2 linkn.2709C>A non_coding_transcript_exon_variant Exon 14 of 14 5
ADGRV1ENST00000639676.1 linkn.1541C>A non_coding_transcript_exon_variant Exon 8 of 11 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
248980
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135058
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461622
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2018
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.Gln1315Lys variant in ADGRV1 has not been previously reported in individua ls with hearing loss or Usher syndrome, but was identified in 1/15284 African ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org; dbSNP rs764685377). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Comp utational prediction tools and conservation analyses do not provide strong suppo rt for or against an impact to the protein. In summary, the clinical significanc e of the p.Gln1315Lys variant is uncertain. ACMG/AMP Criteria applied: PM2. -

not provided Benign:1
Dec 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;T;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.69
.;T;T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.41
T
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.6
.;N;.
REVEL
Benign
0.16
Sift
Benign
0.081
.;T;.
Sift4G
Benign
0.063
.;T;.
Polyphen
0.94
P;P;.
Vest4
0.64
MutPred
0.45
Gain of methylation at Q1315 (P = 0.0093);Gain of methylation at Q1315 (P = 0.0093);.;
MVP
0.55
MPC
0.057
ClinPred
0.32
T
GERP RS
5.4
Varity_R
0.47
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764685377; hg19: chr5-89949334; API